tbuckley/cabot-search huggingface dataset:
Overview of Asian clinical practice guidelines for the management of hepatocellular carcinoma: An Asian perspective comparison
Authors: Yuri Cho, Bo Hyun Kim, Joong-Won Park
Journal: Clinical and Molecular Hepatology (2023)

Hepatocellular carcinoma (HCC) is highly prevalent and the third most common cause of cancer-related death in Asia. In contrast to the West, the main etiology of HCC in many Asian countries except Japan is chronic hepatitis B virus infection. Differences in the major causes of HCC lead to significant clinical and treatment differences. This review summarizes and compares guidelines on managing HCC from China, Hong Kong, Taiwan, Japan, and South Korea. From oncology and socio-economic perspectives, factors such as underlying diseases, staging methods, government policies, insurance coverage, and medical resources contribute to varying treatment strategies among countries. Furthermore, the differences in each guideline are fundamentally caused by the lack of incontrovertible medical evidence, and even existing results of clinical trials can be interpreted differently. This review will provide a complete overview of the current Asian guidelines for HCC in recommendations and in practice.
Abnormal karyotype is an independent predictor of inferior survival in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Authors: Mostafa Abdallah, Kristen McCullough, Rimal Ilyas, Kebede H. Begna, Aref Al-Kali, Mark R. Litzow, William J. Hogan, Abhishek Mangaonkar, Hassan Alkhateeb, Mithun V. Shah, Michelle A. Elliott, James M. Foran, Talha Badar, Jeanne M. Palmer, Cecilia Arana Yi, Lisa Sproat, Animesh Pardanani, Mrinal M. Patnaik, Horatiu Olteanu, Rhett P. Ketterling, Ayalew Tefferi, Naseema Gangat
Journal: Blood Cancer Journal (2023)

suggest an independent prognostic impact of karyotype and ASCT in patients with BPDCN.
Abstracts FT
Journal: Allergy (2023)

Background: Patients with severe, uncontrolled asthma experience poor symptom control and health-related quality of life (HRQoL).Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin (TSLP).In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced exacerbations and improved lung function, asthma control and HRQoL versus placebo in patients with severe, uncontrolled asthma.This analysis assessed the proportion of patients in NAVIGATOR who achieved a 'super response' in patient-reported outcome (PRO) measures of asthma control, asthma symptoms and HRQoL, and who achieved well-controlled or partially controlled symptoms. Method: NAVIGATOR was a multicentre, randomized, double-blind, placebo-controlled study.Patients (12-80 years old) receiving medium-orhigh-doseinhaledcorticosteroidsand ≥1additionalcontroller medication with or without oral corticosteroids were randomized 1:1toreceivetezepelumab210 mgorplacebosubcutaneouslyevery 4 weeks for 52 weeks.The proportions of patients who achieved super-responses in PROs, defined as a change from baseline of at least twice the minimum clinically important difference (MCID) for Asthma Control Questionnaire 6 (ACQ-6; twice MCID, 1.0), Asthma Quality of Life Questionnaire (standardized) for patients aged 12 years and older (AQLQ[S] + 12; 1.0),Asthma Symptom Diary (ASD; 1.0) and St George's Respiratory Questionnaire (SGRQ; 8) scores were assessed.ACQ-6 score was used to assess the proportion of patients who achievedwell-controlled(≤0.75)orpartiallycontrolled(>0.75to<1.5)asthma symptoms.Results: Overall, 528 patients received tezepelumab and 531 received placebo.A higher proportion of tezepelumab-treated patients than placebo-treated patients achieved twice the MCID at week 52 for ACQ-6score(72.6%vs.59.7%),AQLQ(S) + 12score(64.2%vs.52.5%), weekly mean ASD score (31.8% vs. 26.6%)and SGRQ total score (75.3% vs. 62.5%), and at the first post-treatment timepoint assessed (Table1).Over52 weeks,ahigherproportionoftezepelumabrecipients than placebo recipients had well-controlled or partially controlled asthma symptoms (Figure 1).Conclusion: Tezepelumab treatment resulted in a greater proportion of patients achieving early and sustained clinically meaningful improvements in PRO measures of asthma control, asthma symptoms and HRQoL, further demonstrating the efficacy of tezepelumab in patients with severe, uncontrolled asthma.
Abstracts ORAL
Journal: Allergy (2023)

AllergyVolume 78, Issue S111 p. 39-55 Abstracts ORAL Abstracts ORAL First published: 12 March 2023 https://doi.org/10.1111/all.15615Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume78, IssueS111Special Issue: Abstracts from the European Academy of Allergy and Clinical Immunology Hybrid Congress, 1-3 July 2022February 2023Pages 39-55 RelatedInformation
Abstracts Poster
Authors: Subcutaneous immunotherapy (SCIT) is a well-established method of treatment of allergic rhinitis (AR) resulting in symptoms and pharmacotherapy reduction, and better quality of life. However, mechanisms of allergen tolerance induction during SCIT have not been fully understood. miRNAs are important epigenetic mechanism of regulating gene expression and may play a significant role in the process of regaining tolerance.
Journal: Allergy (2023)

AllergyVolume 78, Issue S111 p. 56-716 ABSTRACT Abstracts Poster First published: 12 March 2023 https://doi.org/10.1111/all.15616Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume78, IssueS111Special Issue: Abstracts from the European Academy of Allergy and Clinical Immunology Hybrid Congress, 1-3 July 2022February 2023Pages 56-716 RelatedInformation
Sonodynamic-immunomodulatory nanostimulators activate pyroptosis and remodel tumor microenvironment for enhanced tumor immunotherapy
Authors: Zhuang Chen, Weijing Liu, Zuo Yang, Yi Luo, Chaoqiang Qiao, Anna Xie, Qian Jia, Peng Yang, Zhongliang Wang, Ruili Zhang
Journal: Theranostics (2023)

Rationale: Spatiotemporal control of pyroptosis has a profound impact on cancer immunotherapy.Owing to the precise spatiotemporal control and reduction in the side effects of ultrasound (US), sonodynamic therapy (SDT) is expected to be a promising mean to activate pyroptosis.Furthermore, the pyroptosis-initiated immune response can be amplified by enhanced lymphocyte infiltration occurring due to extracellular matrix (ECM) depletion.Therefore, it is highly desirable to develop a sonodynamic-immunomodulatory strategy to amplify pyroptosis-mediated tumor immunotherapy by remodeling of the tumor microenvironment, thereby enhancing tumor immunotherapy.Methods: We reported a potent strategy based on a sonosensitizer, which is composed of LY364947-loaded porous coordination network (PCN-224) camouflaged with a red blood cell (RBC) membrane and evaluated pyroptosis activation, collagen depletion, immunocyte infiltration, and adaptive immune response during the pyroptosis-initiated immune response in vitro and in vivo.Results: The sonosensitizer generated reactive oxygen species (ROS) under US irradiation and initiated the caspase-3 apoptotic signaling pathway, which is regarded as the key upstream activator of gasdermin E (GSDME)-mediated pyroptosis.During the subsequent anti-tumor immune response mediated by pyroptosis, LY364947 loosened the ECM structure via collagen depletion, resulting in enhanced T-lymphocyte infiltration and nearly complete eradication of tumors in a mouse model with the formation of immunological memory. Conclusion:Our findings indicate that sonodynamic-immunomodulatory pyroptotic strategy exhibits robust anti-tumor immune efficacy as well as provides novel insights into the role of pyroptosis in cancer immunology.
The delta subunit of the GABA<sub>A</sub> receptor is necessary for the GPT2-promoted breast cancer metastasis
Authors: Na Li, Xiang Xu, Dan Liu, Jiaxin Gao, Ying Gao, Xufeng Wu, Huiming Sheng, Qun Li, Jun Mi
Journal: Theranostics (2023)

Objectives: Glutamic pyruvate transaminase (GPT2) catalyzes the reversible transamination between alanine and α-ketoglutarate (α-KG) to generate pyruvate and glutamate during cellular glutamine catabolism. The glutamate could be further converted to γ-aminobutyric acid (GABA). However, the role of GPT2 in tumor metastasis remains unclear. Methods: The wound healing and transwell assays were carried out to analyze breast cancer cell migration and invasion in vitro. Gene ontology analysis was utilized following RNA-sequencing to discover the associated molecule function. The mass spectrometry analysis following phosphoprotein enrichment was performed to discover the associated transcription factors. Most importantly, both the tail vein model and Mammary gland conditional Gpt2-/- spontaneous tumor mouse models were used to evaluate the effect of GPT2 on breast cancer metastasis in vivo. Results: GPT2 overexpression increases the content of GABA and promotes breast cancer metastasis by activating GABAA receptors. The delta subunit GABRD is necessary for the GPT2/GABA-induced breast cancer metastasis in xenograft and transgenic mouse models. Gpt2 knockout reduces the lung metastasis of the genetic Gpt2-/- breast cancer in mice and prolongs the overall survival of tumor burden mice. Mechanistically, GPT2-induced GABAA receptor activation increases Ca2+ influx by turning on its associated calcium channel, and the surged intracellular calcium triggers the PKC-CREB pathway activation. The activated transcription factor CREB accelerates breast cancer metastasis by upregulating metastasis-related gene expressions, such as PODXL, MMP3, and MMP9. Conclusion: In summary, this study demonstrates that GPT2 promotes breast cancer metastasis through up-regulated GABA activation of GABAAR-PKC-CREB signaling, suggesting it is a potential target for breast cancer therapy.
Role of p53 in breast cancer progression: An insight into p53 targeted therapy
Authors: Charlie Marvalim, Arpita Datta, Soo Chin Lee
Journal: Theranostics (2023)

The transcription factor p53 is an important regulator of a multitude of cellular processes.In the presence of genotoxic stress, p53 is activated to facilitate DNA repair, cell cycle arrest, and apoptosis.In breast cancer, the tumor suppressive activities of p53 are frequently inactivated by either the overexpression of its negative regulator MDM2, or mutation which is present in 30-35% of all breast cancer cases.Notably, the frequency of p53 mutation is highly subtype dependent in breast cancers, with majority of hormone receptor-positive or luminal subtypes retaining the wild-type p53 status while hormone receptor-negative patients predominantly carry p53 mutations with gain-of-function oncogenic activities that contribute to poorer prognosis.Thus, a two-pronged strategy of targeting wild-type and mutant p53 in different subtypes of breast cancer can have clinical relevance.The development of p53-based therapies has rapidly progressed in recent years, and include unique small molecule chemical inhibitors, stapled peptides, PROTACs, as well as several genetic-based approaches using vectors and engineered antibodies.In this review, we highlight the therapeutic strategies that are in pre-clinical and clinical development to overcome p53 inactivation in both wild-type and mutant p53-bearing breast tumors, and discuss their efficacies and limitations in pre-clinical and clinical settings.
Cytokine engineered NK-92 therapy to improve persistence and anti-tumor activity
Authors: Hyun Young Shin, Seil Jang, Hyeong Jung Woo, Jae-Hee Chung, Woon-Hae Kim, Dongoh Kim, Minju Kang, Yujin Lim, Omer Habib, Jungmin Lee, Sohae Yang, Dae Hee Lee, Minseok S. Kim
Journal: Theranostics (2023)

Natural killer (NK) cells are an attractive cell source in cancer immunotherapy due to their potent antitumor ability and promising safety for allogenic applications.However, the clinical outcome of NK cell therapy has been limited due to poor persistence and loss of activity in the cytokine-deficient tumor microenvironment.Benefits from exogenous administration of soluble interleukin-2 (IL-2) to stimulate the activity of NK cells have not been significant due to cytokine consumption and activation of other immune cells, compromising both efficacy and safety.Methods: To overcome these drawbacks, we developed a novel membrane-bound protein (MBP) technology to express IL-2 on the surface of NK-92 cells (MBP NK) inducing autocrine signal for proliferation without IL-2 supplementation. Results:The MBP NK cells exhibited not only improved proliferation in IL-2 deficient conditions but also stronger secretion of cytolytic granules leading to enhanced anti-tumor activity both in vitro and in vivo.Furthermore, the experiment with a spheroid solid tumor model exhibited enhanced infiltration by MBP NK cells creating higher local effector-to-target ratio for efficient tumor killing.These results suggest MBP technology can be an effective utility for NK-92 cell engineering to increase anti-tumor activity and reduce potential adverse effects, providing a higher therapeutic index in clinical applications.
Strategies targeting PD-L1 expression and associated opportunities for cancer combination therapy
Authors: Shuangneng Yin, Zhaojun Chen, Dugang Chen, Dan Yan
Journal: Theranostics (2023)

Immunotherapy has achieved great success recently and opened a new avenue for anti-tumor treatment. Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) are typical immune checkpoints that transmit coinhibitory signals, muting the host immunity. Monoclonal antibodies that block PD-1/PD-L1 axis have benefited many patients with different tumor diseases. However, the objective response rate is still unsatisfactory. In this review, we summarize three strategies targeting PD-L1 based on different forms of PD-L1 and various regulating mechanisms to enhance the therapeutic effect, including blockade of the interaction between PD-L1 and PD-1, downregulation of PD-L1 expression and degradation of mature PD-L1. Thereinto, we describe a variety of materials have been designed to target PD-L1, including antibodies, nanoparticle, peptide, aptamer, RNA, and small molecule. Additionally, we list the drugs with PD-L1 regulation capacity used in clinical and ongoing studies to explore other alternatives for targeting PD-L1 besides anti-PD-L1 monoclonal antibodies. Moreover, we discuss associated opportunities for cancer combination therapy with other modalities such as chemotherapy, radiotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), as these conventional or emerging modalities are capable of increasing the immune response of tumor cells by altering the tumor microenvironment (TME), and would display synergistic effect. At last, we give a brief summary and outlook regarding the research status and future prospect of immunotherapy.
Chromothripsis is correlated with reduced cytotoxic immune infiltration and diminished responsiveness to checkpoint blockade immunotherapy
Authors: Han Chu, Zheng Jin, Jia-nan Cheng, Qingzhu Jia, Bo Zhu, Haoyang Cai
Journal: Theranostics (2023)

Background: Chromothripsis caused massive, clustered genomic rearrangements is prevalent in cancer and is considered a new paradigm for tumorigenesis and progression.In this study, we investigated the association among chromothripsis, anti-tumor immune responses, and responsiveness to immune checkpoint blockade (ICB).Methods: Quantification of immune cell infiltration and functional enrichment of immune-related signaling pathways were performed in the discovery set (n = 9403) and the validation set (n = 1140).we investigated the association between chromothripsis and anti-tumor immune responses.In the immunotherapy cohort, copy number alteration-based chromothripsis scores (CPSs) were introduced to assess the extent of chromothripsis to evaluate its association with responsiveness to ICB.Results: In the discovery set and the validation set, the ratios of CD8 + T cells to Tregs, TAMs, and MDSCs were significantly lower in tumors with chromothripsis (P = 1.5 × 10 -13 , P = 5.4 × 10 -8 , and P = 1.2 × 10 -4 , respectively, TCGA; P = 1.0 × 10 -13 , P = 3.6 × 10 -15 , and P = 3.3 × 10 -3 , respectively, PCAWG).The relevant pathways underlying the antitumor immune effect were significantly enriched in tumors without chromothripsis.Chromothripsis can be used as an independent predictor, and patients with low-CPSs experienced longer overall survival (OS) after immunotherapy [HR, 1.90; 95% confidence interval, 1.10-3.28;P = 0.019].Conclusions: Our findings highlight the reduced cytotoxic immune infiltration in tumors with chromothripsis and enhanced immunosuppression in the tumor microenvironment.Chromothripsis can thus be used as a potential indicator to help identify patients who will respond to ICB, which could complement established biomarkers.
Theranostics application of tumor-initiating cell probe TiY in non-small cell lung cancer
Authors: Yong-An Lee, Chee Chong Jonathan Lek, Gao Rong, Zhengwei Wu, S Shathishwaran, Jia Hui Jane Lee, Wai Leong Tam, Torsten Wuestefeld, Sung-Jin Park, Sangyong Jung, Beomsue Kim, Nam-Young Kang, Young-Tae Chang
Journal: Theranostics (2023)

Background: Tumor-initiating cells (TIC) often elude conventional cancer treatment, which results in metastasis and cancer relapse.Recently, studies have begun to focus on the TIC population in tumors to provide better therapeutic options.Previously, we have reported the successful development of a TIC-specific probe TiY with the binding target as vimentin.While a low concentration of TiY showed a TIC visualization, at a high concentration, TiY induced selective toxicity onto TIC in vitro.In this study, we aim to assess TiY's applicability in theranostics purposes, from in vivo visualization to therapeutic effect toward TIC, in cancer mouse models.Methods: We performed cell experiments with the TIC line model derived from resected primary non-small cell lung cancer (NSCLC) patient tumor.The animal model studies were conducted in mice of NSCLC patient-derived xenograft (PDX).TiY was intravenously delivered into the mice models at different concentrations to assess its in vivo TIC-selective staining and therapeutic effect.Results: We demonstrated the TIC-selective identification and therapeutic effect of TiY in animal models.TiY treatment induced a significant ablation of the TIC population in the tumor, and further molecular study elucidated that the mechanism of TiY is through vimentin dynamics in TIC. Conclusion:The results underscore the applicability of TiY for cancer treatment by selectively targeting soluble vimentin in TIC.
GLSP and GLSP-derived triterpenes attenuate atherosclerosis and aortic calcification by stimulating ABCA1/G1-mediated macrophage cholesterol efflux and inactivating RUNX2-mediated VSMC osteogenesis
Authors: Guobin Zheng, Yun Zhao, Zhenhao Li, Yunqing Hua, Jing Zhang, Yaodong Miao, Yang Guo, Lan Li, Jia Shi, Zhengwei Dong, Shu Yang, Guanwei Fan, Chuanrui Ma
Journal: Theranostics (2023)

Background and Purpose: Atherosclerosis is the main pathophysiological foundation of cardiovascular disease, which was caused by inflammation and lipid metabolism disorder, along with vascular calcification.Aortic calcification leads to reduced plaque stability and eventually causes plaque rupture which leads to cardiovascular events.Presently, the drug to treat aortic calcification remains not to be available.Ganoderma lucidum spore powder (GLSP) is from Ganoderma lucidum which is a Traditional Chinese Medicine with the homology of medicine and food.It has multiple pharmacological effects, but no research on aortic calcification during atherosclerosis was performed.This study investigated the effects of GLSP on atherosclerosis and aortic calcification and revealed the underlying mechanism.Methods: In vivo, 8-week-aged male LDLR -/-mice were fed a high-fat diet to induce atherosclerosis along with aortic calcification.Simultaneously, the mice were treated with GLSP at the first week of HFD feeding to determine the protection against early and advanced atherosclerosis.Subsequently, the mice tissues were collected to evaluate the effects of GLSP on atherosclerosis, and aortic calcification, and to reveal the underlying mechanism.In vitro, we determined the major components of GLSP triterpenes by HPLC, and subsequently assessed the protective effects of these main active components on lipid metabolism, inflammation, and calcification in RAW264.7 and HASMC cells.Results: We observed GLSP attenuated plaque area and aortic calcification in the mice with early and advanced atherosclerosis.GLSP reduced the number of foam cells by improving ABCA1/G1-mediated cholesterol efflux in macrophages.In addition, GLSP protected against the aortic endothelium activation.Moreover, GLSP inhibited aortic calcification by inactivating RUNX2-mediated osteogenesis in HASMCs.Furthermore, we determined the major components of GLSP triterpenes, including Ganoderic acid A, Ganoderic acid B, Ganoderic acid C6, Ganoderic acid G, and Ganodermanontriol, and found that these triterpenes promoted ABCA1/G1-mediated cholesterol efflux and inhibited inflammation in macrophage, and inactivated RUNX2-mediated osteogenesis in VSMC.Conclusions: This study demonstrates that GLSP attenuates atherosclerosis and aortic calcification by improving ABCA1/G1-mediated cholesterol efflux and inactivating RUNX2-mediated osteogenesis in Ivyspring
WT1<sup>+</sup> glomerular parietal epithelial progenitors promote renal proximal tubule regeneration after severe acute kidney injury
Authors: Xizhen Hong, Hao Nie, Juan Deng, Shiting Liang, Liting Chen, Jing Li, Siqiao Gong, Guobao Wang, Wei Zuo, Fanfan Hou, Fujian Zhang
Journal: Theranostics (2023)

Rationale: Mammalian renal proximal tubules can partially regenerate after acute kidney injury (AKI). However, cells participating in the renal proximal tubule regeneration remain to be elucidated. Wilms' tumor 1 (WT1) expresses in a subtype of glomeruli parietal epithelial cells (PECs) in adult kidneys, it remains unclear whether these WT1+ PECs play a role in renal regeneration/repair after AKI. Methods: Ischemia-reperfusion injury (IRI) mouse model was used to investigate the expression pattern of WT1 in the kidney after severe AKI. Conditional deletion of WT1 gene mice were generated using Pax8CreERT2 and WT1fl/fl mice to examine the function of WT1. Then, genetic cell lineage tracing and single-cell RNA sequencing were performed to illustrate that WT1+ PECs develop into WT1+ proximal tubular epithelial cells (PTECs). Furthermore, in vitro clonogenicity, direct differentiation analysis and in vivo transplantation were used to reveal the stem cell-like properties of these WT1+ PECs. Results: The expression of WT1 protein in PECs and PTECs was increased after severe AKI. Conditional deletion of WT1 gene in PTECs and PECs aggravated renal tubular injury after severe AKI. WT1+ PECs develop into WT1+ PTECs via the transient scattered tubular cell stage, and these WT1+ PECs possess specific stem cell-like properties. Conclusions: We discovered a group of WT1+ PECs that promote renal proximal tubule regeneration/repair after severe AKI, and the expression of WT1 in PECs and PTECs is essential for renal proximal tubule regeneration after severe kidney injury.